Proton magnetic resonance spectroscopy studies have studied brain levels of creatine-containing compounds. Kato et al (1992) reported that phosphocreatine was significantly decreased in severely (as opposed to mildly) depressed patients. Dager et al (2004) studied depressed or mixed-state bipolar patients using two-dimensional proton echo-planar spectroscopic imaging, reporting an inverse correlation between severity of depression and white matter creatine levels.